前蛋白转化酶枯草溶菌素/克新9型抑制剂对脂蛋白(a)的影响：随机对照试验的荟萃分析和荟萃回归
Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a): A Meta-Analysis and Meta-Regression of Randomized Controlled Trials.
作者信息
Rivera Frederick Berro, Cha Sung Whoy, Linnaeus Louisse Cruz, Carado Genquen Philip, Magalong John Vincent, Tang Vincent Anthony, Enriquez Mary Grace, Gulati Martha, Enkhmaa Byambaa, Pagidipati Neha, Shah Nishant P
机构信息
Department of Medicine, Lincoln Medical Center, New York, New York, USA.
Department of Medicine, Cebu Institute of Medicine, Cebu City, Philippines.
出版信息
JACC Adv. 2025 Jan 10;4(2):101549. doi: 10.1016/j.jacadv.2024.101549. eCollection 2025 Feb.
BACKGROUND
Lipoprotein(a) [Lp(a)] has been independently associated with increased cardiovascular risk.
OBJECTIVES
The authors examined the effect of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) on plasma Lp(a) levels across multiple trials.
METHODS
Studies were retrieved comparing the effect of PCSK9i vs placebo on Lp(a) levels. The primary outcome was percent change in Lp(a) levels. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences.
RESULTS
PCSK9i reduced Lp(a) levels on average of -27% (95% CI: -29.8% to -24.1%, < 0.001). Factors associated with the treatment effect included mean percent change in low-density lipoprotein cholesterol ( = 0.003, beta coefficient 0.34, 95% CI: 0.11-0.57, tau = 94.8, R = 11.82) and apolipoprotein B ( < 0.002, beta coefficient 0.4, 95% CI: 0.14-0.64, tau = 93.68, R = 11.86). Subgroup analyses revealed consistent treatment effect amongst comparators vs placebo: -27.69% (95% CI: -30.85% to -24.54%, < 0.001), vs ezetimibe: -24.0% (95% CI: -29.95% to -18.01%, < 0.001), type of PCSK9i, evolocumab: -29.35% (95% CI: -33.56% to -25.14%, < 0.001) vs alirocumab: -24.50% (95% CI: -27.96% to -21.04%, < 0.001), and presence of familial hypercholesterolemia: -25.63% (95% CI: -31.96% to -19.30%, < 0.001 vs no familial hypercholesterolemia: -27.22%; 95% CI: -30.34% to -24.09%, < 0.001). Varying treatment effects were noted in the duration of treatment (12 weeks or shorter: -32.43% [95% CI: -36.63% to -28.23% vs >12 weeks: -22.31%] [95% CI: -25.13% to -19.49%, < 0.001]), interaction < 0.01.
CONCLUSIONS
PCSK9is reduce Lp(a) levels by an average of 27%. Mean percent change in low-density lipoprotein cholesterol and apolipoprotein B were associated with treatment effect.
背景
脂蛋白(a)[Lp(a)]与心血管疾病风险增加独立相关。
目的
作者在多项试验中研究了单克隆抗体前蛋白转化酶枯草溶菌素/ kexin 9型抑制剂(PCSK9is)对血浆Lp(a)水平的影响。
方法
检索比较PCSK9i与安慰剂对Lp(a)水平影响的研究。主要结局是Lp(a)水平的变化百分比。通过meta回归分析确定与治疗效果相关的因素。进行亚组分析以探索潜在的治疗效果差异。
结果
PCSK9i使Lp(a)水平平均降低-27%(95%CI：-29.8%至-24.1%，<0.001)。与治疗效果相关的因素包括低密度脂蛋白胆固醇的平均变化百分比(=0.003，β系数0.34，95%CI：0.11-0.57，tau = 94.8，R = 11.82)和载脂蛋白B(<0.002，β系数0.4，95%CI：0.14-0.64，tau = 93.68，R = 11.86)。亚组分析显示，与安慰剂相比，各比较组的治疗效果一致：-27.69%(95%CI：-30.85%至-24.54%，<0.001)，与依折麦布相比：-24.0%(95%CI：-29.95%至-18.01%，<0.001)，PCSK9i类型，阿利西尤单抗：-29.35%(95%CI：-33.56%至-25.14%，<0.001)与阿利西尤单抗：-24.50%(95%CI：-27.96%至-21.04%，<0.001)，以及家族性高胆固醇血症的存在：-25.63%(95%CI：-31.96%至-19.30%，<0.001)与无家族性高胆固醇血症：-27.22%；95%CI：-30.34%至-24.09%，<0.001)。在治疗持续时间方面观察到不同的治疗效果(12周或更短：-32.43%[95%CI：-36.63%至-28.23%]与>12周：-22.31%][95%CI：-25.13%至-19.49%，<0.001])，交互作用<0.01。
结论
PCSK9is使Lp(a)水平平均降低27%。低密度脂蛋白胆固醇和载脂蛋白B的平均变化百分比与治疗效果相关。
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